This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project Description: The long-term goal of this project is to elucidate the roles of fluid and solute transport in tissue mechanical function and cell nutrition of the human TMJ disc for delineating the biomechanical etiology of TMDs and to develop new strategies for restoring tissue function. The specific aims of this proposal are to: 1) evaluate the effect of mechanical strain on the transport properties of the human TMJ disc and develop constitutive relationships between transport properties and tissue biochemical composition;2) establish fluid flow dependent mechanisms for disc loading support and lubrication. To accomplish aim 1, we will: a) determine hydraulic permeability, fixed charge density, and electrical conductivity of the normal human TMJ disc under various mechanical strains;b) obtain ion diffusivities from electrical conductivity data and develop new constitutive relationships between transport properties (hydraulic permeability and solute diffusivity) and tissue hydration to establish strain-dependent transport properties. To accomplish aim 2, we will determine time-dependent fluid pressure, fluid load support, and friction coefficient of the normal human TMJ disc under sustained mechanical loading, and correlate fluid load support and friction coefficient to interstitial fluid pressure. These studies will provide new insights into a bio-transport related mechanism for disc degeneration. To achieve our long-term goal, we will further develop a new multiphasic mechano-electrochemical finite element model of the human TMJ disc which will provide details of mechanical stress, strain, fluid pressure, nutrient concentrations, electrical potential, fluid flow, and transport of nutrients within the TMJ disc under physiological or pathological loading conditions. Studies will also be conducted to understand the biological response of disc cells to these physicochemical signals for fully elucidating biomechanical etiology of TMJ disc degeneration.